Retinoic acid, perhaps the most potent hormonal form of the naturally occurring retinoids (retinol and derivatives), is required in vivo for the maintenance of normal pregnancy and embryo development. However, little is known about the specific sites of action and metabolism in the uterus during pregnancy. In this study we describe the pattern of temporal and cell-specific expression of cellular retinol-binding protein (CRBP) and cellular retinoic acid-binding proteins type I and type II (CRABP and CRABP[II], respectively) in the rat uterus during the periimplantation period (Day 1 to Day 7 of pregnancy; Day 1 = presence of vaginal plug). Immunohistochemical studies showed that there were dramatic and rapid changes in expression pattern of the retinoid-binding proteins after mating as early as Day 1, as well as a differential expression of these proteins when the mesometrial side and antimesometrial side of the uterus were examined during the periimplantation period. CRABP(II), whose presence has been previously shown to correlate with retinoic acid synthesis in the uterine epithelium, was specifically localized to the luminal epithelium at Day 1, being stronger on the mesometrial side, and then fell to lower levels. CRBP was also expressed in the luminal epithelium on the mesometrial side at Day 1 as well as in some stromal cells, declining at these sites over the next several days. CRABP was localized to some of the stromal cells at Day 1, overlapping CRBP expression. Embryonic implantation was accompanied by the appearance of CRBP and CRABP(II) in the decidual cells. CRBP and CRABP were also present in both smooth muscle layers of the uterus. The changes in the temporal and cell-specific distribution of retinoid-binding proteins imply a multifunctional role of vitamin A in uterine cell proliferation, differentiation, and embryonic implantation. The presence of CRABP(II) suggests that local generation of retinoic acid is important in these processes.